In general, cardiac pacemakers are electrical devices used to supplant some or all of an abnormal heart's natural pacing function. Pacemakers typically operate to deliver appropriately timed electrical stimulation signals, sometimes called pacing pulses, designed to cause the myocardium to contract or "beat." For state-of-the-art pacemakers, the rate at which stimulation signals are delivered may be variable, and such variation may occur automatically in response to detected changes in a patient's level of physical activity. Such rate- or activity-responsive pacemakers depend on physiologically-based signals, such as signals from sensors measuring the pressure inside the patient's ventricle, for determining a patient's activity level. One popular method for measuring a patient's activity level, and hence the patient's demand for oxygenated blood, is to measure the physical activity of the patient by means of a piezoelectric transducer. Such a pacemaker is disclosed in U.S. Pat. No. 4,485,813 to Anderson et al.
In typical prior art rate-responsive pacemakers, the pacing rate is determined according to the output from an activity sensor. The pacing rate is variable between a predetermined maximum and minimum level, which may be selectable by a physician from among a plurality of programmable upper and lower rate limit settings. When the activity sensor output indicates that the patient's activity level has increased, the pacing rate is increased from the programmed lower rate by an incremental amount which is determined as a function of the output of the activity sensor. That is, the rate-responsive or "target" pacing rate in a rate-responsive pacemaker is determined as follows: EQU Target Rate=Programmed Lower Rate+f(sensor output)
where f is typically a linear or monotonic function of the sensor output. As long as patient activity continues to be indicated, the pacing rate is periodically increased by incremental amounts until the rate computed according to the above formula is reached (or until the programmed upper rate limit is reached, whichever is lower). In this way, an elevated pacing rate (i.e., one higher than the programmed lower rate limit) may be sustained during periods of patient activity. When patient activity ceases, the pacing rate is gradually reduced, until the programmed lower rate limit is reached.
For any of the known rate-responsive pacemakers, it is clearly desirable that the sensor output correlate to as high a degree as possible with the actual metabolic and physiologic needs of the patient, so that the resulting rate-responsive pacing rate may be adjusted to appropriate levels. A piezoelectric activity sensor can only be used to indirectly determine the metabolic need. The physical activity sensed can be influenced by upper body motion. Therefore, an exercise that involves arm motion may provide signals that are inappropriately greater than the metabolic need. Conversely, exercises that stimulate the lower body only, such as bicycle riding, may provide a low indication of metabolic need while the actual requirement is very high.
To address these perceived disadvantages in the prior art, other physiologically-based parameters have been utilized to assess a patient's metabolic demand. Among these parameters are cardiac pressure, blood oxygen saturation, and minute ventilation (V.sub.e), each of which having been demonstrated clinically to be parameters that correlates well with the actual metabolic and physiologic needs of the patient.
Minute ventilation, which has been found to be a very good indicator of a patient's metabolic demand, is defined by the equation: EQU V.sub.e =RR.times.VT
where RR=respiration rate in breaths per minute (bpm), and VT=tidal volume in liters. Clinically, the measurement of V.sub.e is performed by having the patient breathe directly into a device that measures the exchange of air and computes the total volume per minute. The direct measurement of V.sub.e is not practical with an implanted device. However, measurement of the impedance changes of the thoracic cavity can be implemented with an implanted pacemaker. Such a pacemaker is disclosed in U.S. Pat. No. 4,702,253 issued to Nappholz et al. on Oct. 27, 1987. The magnitude of the change of the impedance signal corresponds to the tidal volume and the frequency of change corresponds to respiration rate. Thus, measurement of cardiac impedance can be used as one method for obtaining V.sub.e data.
In practice, cardiac impedance can be measured through assessment of the impedance present between two or more cardiac electrodes, such as the electrodes otherwise used for pacing and/or sensing in connection with a cardiac pacemaker. In particular, it has been shown that cardiac impedance can be measured by delivering constant-current excitation pulses between two "source" electrodes, such that the current is conducted through some region of cardiac tissue. The voltage differential between two "recording" electrodes can then be measured to ascertain the impedance as reflected by the voltage differential arising from the conduction of the excitation current pulses through the tissue. Such an impedance measuring technique has proven to be practicable in connection with implantable devices, such as cardiac pacemakers.
In U.S. Pat. No. 4,721,110 to Lampadius, there is described a rheographic arrangement for a cardiac pacemaker in which the base pacing rate of the pacemaker is determined, in part, by a rheographically derived respiration rate signal.
Correlation of breathing and intrathoracic pressure fluctuations with impedance of blood in the heart is also recognized in U.S. Pat. No. 4,884,576 to Alt, which describes the measurement of impedance between two electrodes. According to the Alt '576 patent, low-pass filtering of the impedance signal yields a signal from which the patient's respiratory rate can be derived, while high-pass filtering of the same signal yields a signal from which the patient's cardiac function can be observed.
There are currently several commercially-available implantable devices which employ rheographic techniques to adjust the pacing rate in response to metabolic needs. For example, the Biorate device manufactured by Biotec International, Bologna, Italy, uses a bipolar rheographic arrangement to monitor the patient's respiration rate. The Meta-MV device manufactured by Telectronics, Inc., Englewood, Colo., uses a tripolar rheographic arrangement to monitor the patient's metabolic demand for oxygenated blood. The Precept device manufactured by CPI, St. Paul, Minn., uses a tetrapolar rheographic configuration to monitor the patient's pre-ejection interval (PEI), stroke volume, and heart tissue contractility.
The Legend Plus.TM. pulse generator, manufactured by Medtronic, Inc., Minneapolis, Minn. and currently undergoing clinical trials in the United States, is another example of an implantable pacemaker which employs rheography in support of its activity-response function. The Legend Plus.TM. delivers a biphasic excitation signal between the pulse generator's canister (serving as an indifferent electrode) and a ring electrode of a transvenous pacing/sensing lead. Impedance sensing in the Legend Plus.TM. carried out between the lead's tip electrode and the pulse generator canister. The Legend Plus.TM. impedance measuring circuitry generates an impedance waveform in which both respiration and cardiac systole are reflected. This waveform is used by the pacemaker's circuitry to derive a minute ventilation value V.sub.e, as defined above. The Legend Plus.TM. periodically assesses a patient's V.sub.e, and adjusts its base pacing rate up or down in accordance with the metabolic demand reflected in the V.sub.e value. (Various aspects of the Legend Plus.TM. device are described in U.S. Pat. No. 5,271,395 to Wahlstrand et al. entitled "Method and Apparatus for Rate-Responsive Cardiac Pacing," which patent is hereby incorporated by reference herein in its entirety.)
Another disclosure which relates to the use of rheography in connection with an implanted device can be found in co-pending U.S. patent application Ser. No. 08/233,901 filed on Apr. 28, 1994 in the name of Wahlstrand et al. entitled "Method and Apparatus for Sensing of Cardiac Function", which proposes a method and apparatus for obtaining an impedance waveform. The Wahlstrand et al., disclosure, which relates to the use of a specialized lead for improving the quality of an impedance waveform like that utilized in the aforementioned Legend Plus.TM., is hereby incorporated by reference herein in its entirety.
Yet another disclosure relating to the use of rheography in connection with implantable devices can be found in co-pending U.S. patent application Ser. No. 08/277,051 filed on Jul. 19, 1994 in the name of Gianni Plicchi et al. entitled "Time-Sharing Multi-Polar Rheography".
In an effort to minimize patient problems and to prolong or extend the useful life of an implanted pacemaker, it has become common practice to provide numerous programmable parameters in order to permit the physician to select and/or periodically adjust the desired parameters or to match or optimize the pacing system to the patient's physiologic requirements. The physician may adjust the output energy settings to maximize pacemaker battery longevity while ensuring an adequate patient safety margin. Additionally, the physician may adjust the sensing threshold to ensure adequate sensing of intrinsic depolarization of cardiac tissue, while preventing oversensing of unwanted events such as myopotential interference or electromagnetic interference (EMI). Also, programmable parameters are typically required to enable and to optimize a pacemaker rate response function as described above. Among the pacemakers manufactured by the assignee of the present invention are those that are multiprogrammable and rate-responsive, having numerous programmable parameters, including pacing mode, sensitivity, refractory period, pulse amplitude, pulse width, lower and upper rate limits, rate response gain, and activity threshold.
Those of ordinary skill in the art will appreciate that whether or not a pacemaker operates in a rate-responsive mode, the energy of stimulating pulses it delivers, i.e., the strength (amplitude) and duration (pulse width) of stimulation signals, must be of sufficient magnitude to achieve capture. (As used herein, the term "capture" will be used to refer to the occurrence of a cardiac contraction in direct response to the application of an electrical stimulation signal; to achieve capture is to evoke a cardiac response to delivery of a stimulation signal.) It is imperative that capture be maintained in order to prevent serious complications or even death, especially for those patient's who are partially or wholly dependent upon their pacemakers. At the same time, however, it is desirable for pacemaker stimulation signal energy levels to not be unnecessarily high, as this tends to decrease the useful life of the implanted device due to battery depletion, and can also have undesirable physiological side effects. In recognition of this trade-off between maintaining capture and maximizing device longevity, it has been common practice in the prior art to first determine the minimum energy level necessary to achieve capture in a patient (the patient's "pacing threshold"), and then to pace a patient's heart with pulses having an energy level that is a predetermined safety margin greater than the patient's pacing threshold.
Chief among the problems of ensuring that the safety margin between the energy level of stimulation pulses and a patient's pacing threshold is that stimulation thresholds necessary for maintaining capture often fluctuate in the short term, and can gradually change over the long term. It has been clinically observed that a lower threshold is typically exhibited immediately after implantation of the pacemaker (the so-called "acute threshold"). Inflammation in the tissue around the stimulating electrode generally drives the pacing threshold up sharply to its "peak threshold" level during the first two to six weeks after implant. Over the long term, some of this inflammation reduces, lowering the threshold from its peak to a "chronic threshold" level. The chronic threshold may not reduce to the acute level, however, since some permanent fibrous tissue will develop around the stimulating site, so that greater energy is required than for non-fibrous acute tissue.
In the short term, thresholds may decrease with exercise, for example, and may increase with other activities, including sleep.
Since patient's pacing thresholds vary over time, periodic assessments of a patient's threshold must be made, so that the energy level of stimulation pulses can be adjusted accordingly. One early proposal relating to the assessment of stimulating thresholds and adjusting stimulating levels in response to detected threshold levels can be found in U.S. Pat. No. 3,920,024 to Bowers, entitled "Threshold Tracking System and Method for Stimulating a Physiological System."
Another prior art arrangement for assessing stimulating thresholds is disclosed in U.S. Pat. No. 4,250,884 to Hartlaub et al., entitled "Apparatus For and Method Of Programming the Minimum Energy Threshold for Pacing Pulses to be Applied to a Patient's Heart." The Hartlaub et al. '884 patent is assigned to the assignee of the present invention and is hereby incorporated by reference herein in its entirety.
According to the Hartlaub '884 patent, a pacemaker and programmer are operable to function in a so-called "autothreshold" mode, wherein the pacemaker delivers a series of progressively lower energy level stimulation pulses to the patient's heart. While the pacemaker and programmer are operating in the autothreshold mode, the physician or clinician who initiated the autothreshold function monitors the patient's EKG on a strip-chart or display screen. The physician or clinician takes note of which pulse among the sequence first fails to achieve capture, and in response immediately discontinues the autothreshold test. This identifies to the programmer that the patient's pacing threshold lies between the energy levels of the two most recently delivered pulse, and the programmer can then adjust the level of pacing pulse energy to be at a level which includes at least a predetermined safety margin above the patient's threshold.
Although the method and apparatus disclosed in the Hartlaub '884 reference provides a means for determining a patient's pacing threshold so that battery depletion is minimized and patient safety is ensured, the Hartlaub '884 system requires the presence of a trained physician or clinician to perform the autothreshold procedure, and the autothreshold adjustment must be carried out in a clinical setting. This can be inconvenient and expensive for the patient. To address these issues, attempts have been made in the prior art to provide implantable pulse generators with a more fully automatic threshold detection feature, so that capture can be maintained without the need for clinical or patient intervention. Such IPGs typically rely upon electrical sensors similar to pacing leads to sense the presence of capture in response to the delivery of stimulation signals. However, the function and accuracy of these sensors have been shown to be adversely affected by one or more factors, including (but not limited to): myopotentials (electrical signals which are the product of muscle movement), electromagnetic interference (EMI), problems with sensor sensitivity (either too sensitive or not sensitive enough), and variations in the sense electrical signals as a function of changes in thoracic pressure (for example, due to changes in respiration rate, coughing, or sneezing).
Another difficulty with reliance upon electrical sensing to detect the presence or absence of capture without the necessity of physician intervention is that the sensing circuitry typically is not capable of discriminating between an intrinsic beat which would have occurred even if no stimulation pulse had been delivered, and an actual captured beat.
The above-mentioned and other difficulties associated with automating the procedure for determining a patient's pacing threshold and adjusting the stimulation pulse energy level can be generally described as involving either lack of sensitivity or lack of specificity in capture detection. (As used herein, "sensitivity" in capture detection is used to refer to the ability to avoid false negative capture detection--not recognizing when capture actually occurs--quantified as the number of loss-of-capture beats identified as such divided by the actual number of loss-of-capture beats, over a given time. On the other hand, "specificity" in capture detection refers to the ability avoid false positive capture detection--indicating that capture has occurred when it actually has not--quantified as the number of capture beats identified as such divided by the actual number of capture beats, over a given time.)